POTENTIATION OF ANTINOCICEPTIVE EFFECTS OF MORPHINE BY CALCIUM-CHANNEL BLOCKERS AT THE LEVEL OF THE SPINAL-CORD

Background: opioids inhibit voltage-dependent calcium-channel conducta nce, which is essential for the nervous system to be able to signal a painful event. Accordingly, interference with calcium-channel conducta nce may enhance opioid analgesia. The current study was designed to in vestigate the effects of calcium-channel blocking drugs on the antinoc iception of morphine at the level of the spinal cord. Methods: Rats we re chronically implanted with catheters in the lumbar intrathecal spac e. Tail-flick test was used to assess thermal nociception. Intrathecal ly administered drugs were morphine, calcium-channel blockers (verapam il, diltiazem, and nicardipine), or a combination of morphine and calc ium-channel blocker. Results: Intrathecal administration of morphine p roduced a significant dose-dependent antinociception in the tail-flick test. In contrast, intrathecal administration of calcium-channel bloc kers, verapamil, diltiazem. and nicardipine, did not show any antinoci ception at the employed doses. However, when intrathecally administere d calcium-channel blockers, verapamil (50 mug), diltiazem (100 mug), o r nicardipine (20 mug), were combined with ineffective (0.25. 0.5, 1, or 2 mug) or moderately effective (5 mug) doses of intrathecally admin istered morphine, significant antinociception was produced. These inte ractions were synergistic. There were no significant changes in MAP or HR after the intrathecal administration of 200 mug verapamil or 2 mug morphine combined with 50 mug verapamil. Conclusions: The authors int erpreted these results to indicate that calcium-channel blocking drugs synergistically potentiate the analgesic effects of morphine at the l evel of the spinal cord. Before these results can be translated into c linical use, however, adequate toxicity studies must be conducted to e xamine the effect of the perispinal administration of calcium-channel blocking drugs on spinal cord function.